Osteoporosis, a disease which affects 25 million people in United States, primarily women, is the cause of 1.5 million fractures annually. It is treated or prevented primarily by estrogen replacement therapy. Oral or percutaneous administration may result in a compliance problem since treatment is carried out without interruption for six years or more in postmenopausal women. The aim of this project is to formulate controlled release microparticulate/implant drug delivery systems of estrogen for subcutaneous or intraperitoneal administration, which will deliver 2 to 4 microgram of estrogen daily for at least three months. encapsulated in biodegradable poly(glycolic acid-CO-dl-lactic acid) or poly-dl-lactic acid by non-solvent addition, solvent evaporation and multiple emulsion techniques or prepared as implants. The microparticulate/implants will be characterized, and in vitro release studies in a closed system and an open system mimicking in vivo situation carried out. The microparticulate/implant drug delivery systems will be injected subcutaneously or intraperitoneally into adult female New Zealand white rabbits once, and blood samples taken every seven days for three months for radioimmunoassay using a radioimmunoassay kit. Various formulations will be prepared and tested to achieve this goal.